Natural killer cell reactivity: regulatory interactions and among phorbol ester, interferon, cholera toxin, and retinoic acid
Goldfarb, R.H.; Herberman, R.B.
Journal of Immunology 126(6): 2129-2135
1981
ISSN/ISBN: 0022-1767 PMID: 6164721 Document Number: 170828
The expression of mouse and human natural killer [NK] cells is modulated by several molecules with widespread biologic regulatory potential: the potent tumor promoter phorbol-12-myristate-13-acetate [PB], retinoic acid [RA], cholera toxin [CTX] and interferon [IF]. The tumor-promoting phorbol ester, but not nontumor-promoting structural analogs, inhibited both mouse and human NK cell activity. PB inhibited both spontaneous and IF-augmented mouse NK cell activity, but the effects on the latter varied considerably with the sequence of the treatments. Human peripheral blood lymphocytes and subpopulations enriched for large granular lymphocytes that account for human NK cell activity showed a more variable response to PB: with some donors, spontaneous and IF-boosted NK cell activities were inhibited, but with others only the boosted activity was affected. RA enhanced NK cell activity, and this augmented activity was also inhibited by the tumor promoter. Combined treatment with RA and IF produced less augmentation than either agent alone. CT strongly inhibited spontaneous and augmented NK cell activity. Subunits A or B of CT lacked the capacity to inhibit spontaneous or IF-augmented NK activity. Apparently NK cell activity is subject to regulation by a variety of physiologically active agents. It is of both biologic interest and of potential significance that a tumor promoter inhibits NK cell activity whereas RA, a tumor preventive agent, enhances NK cell activity. The possible nature of the interactions among these agents and the potential in vivo relevance of the observed effects of the tumor promoter are discussed.